Project Summary Thirdhand smoke (THS) is the persistent residue resulting from secondhand smoke (SHS) that accumulates in dust, in objects, and on surfaces in homes where tobacco has been used. Smokers' homes become reservoirs of persistent toxic pollutants (e.g., nicotine, polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA)). Some THS pollutants continue to undergo further chemical changes in the home (e.g., nicotine to TSNAs). Children are exposed to THS toxicants via inhalation, dermal transfer, and ingestion of compounds from indoor reservoirs, and we recently demonstrated that children of smokers carry THS pollutants on their hands. Children are up to 100 times more sensitive to dust pollutants than adults. Even in homes with smoking bans, children have 5-7 times more nicotine exposure than children in nonsmoking homes. Nicotine and TSNA exposure from THS can be 6.8 and 16 times higher in toddlers, respectively, than what would be inhaled through SHS, and there is concern that THS causes hazardous health effects in children. Very little is known about the extent to which THS contributes to children's overall levels of tobacco smoke exposure (OTS), defined as their combined THS and SHS exposure. Even less is known about the effect of OTS and THS on child health. Building on prior research and leveraging the experimental design from an active tobacco cessation trial of caregivers who smoke and their children (R01HD083354), we propose the first project to examine how different home smoking behaviors contribute to THS and OTS. Our hypothesis is that independent of SHS, THS contributes significantly to OTS such that higher levels of THS pollutants in the home are associated with higher levels of THS exposure in children and that THS persists even after smokers quit. Further, we hypothesize that higher levels of THS exposure are associated with respiratory-related diagnoses, interventions, and positive test results. We will test these hypotheses within three aims using hand wipe, urine, air, and dust samples and medical record review of children before and 6-weeks and 6-months after a cessation intervention. Biological and environmental samples will become part of a unique repository for future research. Our aims are: 1) To examine the contribution of THS in children's environments to their OTS exposure; 2) To determine the levels and composition of THS pollutants in house dust in smokers' homes 6- months after a cessation intervention; and 3) To examine factors associated with THS and OTS levels and to explore if these levels are associated with increased rates of respiratory illness (e.g., asthma). If our hypotheses are supported, our findings will be crucial to help close gaps in our understanding of the types, quantity, and clinical effects of OTS, THS exposure, and THS pollutants in a unique sample of smoke exposed ill children and their homes. The potential impact of these findings is substantial, as currently the level of risk attributable to THS is unknown. This research has the potential to change how we protect children from OTS, by recognizing that SHS and THS needs to be addressed separately as sources of pollution and exposure.